Poly(ADP-ribose) synthetase is a chromatin bound enzyme that adds chains of ADP-ribose in tandem to nuclear proteins. This enzyme is activated by DNA damaging agents such as gamma, x-ray and u.v. irradiation and by DNA alkylating agents. We have synthesized and tested 6 compounds which are inhibitors of the synthetase and found that the ability of 4 of 6 of them to block DNA repair is directly correlated with the compound's potency as a synthetase inhibitor. The compounds ranked in order of their ability to block DNA repair are 3-acetlaminobenzamide greater than 3-hydroxybenzamide = benzamide greater than to 3-aminobenzamide. 3-nitrobenzamide was found to be much more inhibitory for the repair of DNA chain breaks than was expected based on its potency as a poly(ADP-ribose) synthetase inhibitor. Plots of the reciprocal of the repair velocity vs inhibitor concentration normalized against its ki for synthetase were made. These plots were biphasic indicating that the benzamides had effects on more than one cellular process. At least two processes other than DNA repair have been implicated as targets. These are RNA synthesis and glutamine synthetase. The latter enzyme was found to be an acceptor protein for mono-ADP-ribose. The enzyme catalyzing this reaction was also found to be inhibited by the benzamides, though their potency as inhibitors for this enzyme was much less than their potency as synthetase inhibitors.